2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 86763415, compound

HRID 2201523Notes

Reaction equation

HRID 2201523 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[C:7](=[O:19])[C:6]=2[N:20]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][C:30]3[CH:40]=[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])[C:38](B4OC(C)(C)C(C)(C)O4)=[CH:37][C:31]=3[C:32]=2[C:33]([NH:35][CH3:36])=[O:34])=[CH:24][CH:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:8]2[C:7](=[O:19])[C:6]3[N:20]=[C:2]([C:38]4[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])=[CH:40][C:30]5[O:29][C:28]([C:25]6[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=6)=[C:32]([C:33]([NH:35][CH3:36])=[O:34])[C:31]=5[CH:37]=4)[CH:3]=[CH:4][C:5]=3[O:10][CH2:9]2)=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 117801547HCID 117801547, compound

Product 1

HCID 86763415HCID 86763415, compoundYield 89.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

To a solution of 6-bromo-3-(4-fluorobenzyl)-2H-pyrido[2,3-e][1,3]oxazin-4(3H)-one (110 mg, 0.33 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (149 mg, 0.30 mmol) and K3PO4.3H2O (237 mg, 0.89 mmol) in dioxane/H2O (5 mL/0.2 mL) were added Pd2(dba)3 (13 mg, 0.02 mmol) and X-phos (14 mg, 0.03 mmol) under N2. The mixture was stirred at 110° C. for 1 hour. Then it was filtered and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash gel chromatography (DCM:MeOH=100:1) to afford the product of 5-(3-(4-fluorobenzyl)-4-oxo-3,4-dihydro-2H-pyrido[2,3-e][1,3]oxazin-6-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (170 mg, yield: 82%). 1H-NMR (CDCl3, 400 MHz) δ 7.94˜7.97 (m, 3H), 7.75˜7.77 (m, 1H), 7.62 (s, 1H), 7.42˜7.45 (m, 1H), 7.33˜7.36 (m, 2H), 7.19 (t, J=7.6 Hz, 2H), 7.05 (t, J=7.6 Hz, 2H), 6.05 (br s, 1H), 5.22 (s, 2H), 4.78 (s, 2H), 3.22 (s, 3H), 2.99 (d, J=4.8 Hz, 3H), 2.93 (s, 3H). MS (M+H)+: 633.

Workup

  1. filtrationThen it was filtered
  2. extractionextracted with EtOAc
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash gel chromatography (DCM:MeOH=100:1)

Sources & evidence

ORD record
ord-048b85de3329450daffc3c4c3586d8c2
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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